Adapted from Applicant's Abstract) PI G. Lutty will investigate the effect of the cytokines IL-1 and TNFalpha which up-regulate adhesion molecules on retention of human sickle erythrocytes in the retinal microvasculature in a rat model in which only SS4 cells (dense SS cells) are retained under normal conditions. A second hypothesis will be investigated that transgenic mice with higher levels of expression of human alpha and BetaS- globin genes have an earlier onset and more severe retinopathy and that the onset of vaso-occlusion occurs more rapidly if the animals receive LPS, which may stimulate up-regulation of adhesion molecules by mechanisms similar to those observed in the rat model.